JPH05286824A - Liposome-containing cosmetic - Google Patents

Abstract

PURPOSE:To provide the subject safe cosmetic stable for a long period of time, excellent in the absorbability for the active ingredient and the sustainability of its effect. CONSTITUTION:The objective cosmetic formulated with a liposome with the constituent being dialkyl-type phospholipid and/or its derivative of the formula (R<1>-R<3> are each H or lower alkyl), a form of old bacterial lipids, capable of mass synthesis and industrial production (e.g. 1,2-di-O-phytanyl-glycero- phosphocholine; where, R<1>=R<2>=R<3>=CH3). This liposome is excellent in both thermal stability and preservability compared with conventional liposomes consisting of diacyl-type phospholipids having been generally used, being also stable to the change in pH and osmotic pressure and to physiologically active substances, etc. Besides, this liposome, like conventional ones, has percutaneous absorption effect and such effect's sustainability, and the phospholipid as the constituent is also high in biocompatibility. For the present liposome, any substance having effects as cosmetics, such as humectant effect, skin whitening effect, aging-preventive effect, dermal cell-activating effect, or ultraviolet light absorption or screening effect, can be used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cosmetic composition, and more particularly to a cosmetic composition containing a liposome encapsulating a component having a moisturizing effect or various active ingredients for absorption into the skin.

[0002]

2. Description of the Related Art In recent years, mineral water, hormones, vitamins,
BACKGROUND ART Photosensitizers, plant / animal extract components, UV absorbers, and various other effective substances that promote skin regeneration and recovery are incorporated into cosmetics. However, among these substances, there are substances that are difficult to mix with cosmetics, very unstable substances, and substances that have low absorbability to the skin, and substances that do not exhibit their full effect. Many.

On the other hand, phospholipids, which are bio-derived components, have properties such as surface-active / emulsifying properties, wetting / nutritive effects, and low irritation to living organisms. It is widely used as a moisturizer, touch improver, etc. In addition, liposomes formed from phospholipids are attracting attention for their role as carriers for various drugs, and by encapsulating the above-mentioned active substance inside the liposomes, it is possible to improve their activity, stability, and absorbability. Instead, it is known to have the effect of adding durability.

However, when such liposomes are blended in cosmetics, the liposomes themselves are
Since it is unstable to changes in pH and osmotic pressure and various physiologically active substances, it is difficult to mix it with cosmetics in which many compounds coexist, and the conditions for encapsulating the active ingredient are limited. Furthermore, it has many problems such as lack of long-term stability, and its use is currently very limited.

[0005]

SUMMARY OF THE INVENTION Therefore, the present invention provides a liposome containing various active substances, excellent in absorption of the active ingredient and long-lasting effect, and having long-term stability, and cosmetics containing the same. The purpose is to provide.

In order to solve the above problems, the present invention provides
As a liposome-forming material, we focused on the phospholipids that make up the cell membrane of archaea. In general, a group of bacteria called archaea that live in extreme environments is different from normal organisms.
It is known that an alkyl group, a terpenoid group, a polyisoprenoid group or the like has a phospholipid in which a glycerol moiety is ether-bonded. The peculiarity of its structure has been thought to be one of the reasons why archaea can live in extreme environments such as high temperature, high pressure, and high salt concentration, but it has been difficult to obtain archaeal lipids in large quantities by extraction or synthesis. , Its characteristics were not well revealed. Therefore, the archaeal lipid is hardly applied and industrially used at present. However, in one form of archaeal lipid, the formula (I):

[0007]

[Chemical 2]

The diphytanyl glycerophospholipid represented by the formula (in the formula, R ¹ , R ² and R ³ each represent a hydrogen atom or a lower alkyl group) has become possible for large-scale synthesis and industrial production (Japanese Patent Application No. Hei 10 (1999) -135242). 3-262142), the present inventor has conducted various studies on its properties and application fields, and the liposome composed of this phospholipid is extremely stable, and the liposome composed of this diphytanylglycerophospholipid for cosmetic use. The inventors have found that the above problems can be solved by using, and have completed the present invention.

[0009]

The present invention has the general formula (I):

[0010]

[Chemical 3]

A cosmetic comprising a phospholipid represented by the formula (wherein R ¹ , R ² , and R ³ each represent a hydrogen atom or a lower alkyl group) or a liposome having a derivative thereof as a constituent. Regarding

[0012]

EXAMPLE In the cosmetic of the present invention, the archaeal membrane lipid represented by the above formula (I) and / or its derivative is used as a constituent of the liposome contained therein. This phospholipid is
It is a dialkyl type phospholipid in which a phytanyl group is ether-bonded to a glycerol moiety, and there are various forms having different polar group moieties. R ¹ , R ² and R in formula (I)
³ is a hydrogen atom or 1 to 6 carbon atoms, preferably 1 to 4
Is a linear or branched lower alkyl group. Specific examples of the phospholipid include 1,2-di-O-phytanyl-
Glycero-phosphocholine (in the general formula (I), R ¹ = R
_{^{2 = R 3 = CH 3)}} , 1,2- di -O- phytanyl - glycero -N- methyl - phosphoethanolamine (formula
In (I), R ¹ = R ² = H, R ³ = CH ₃ ), 1, 2
-Di-O-phytanyl-glycero-N, N-dimethyl-
Phosphoethanolamine (in the general formula (I), R ¹ =
^{H, R 2 = R 3 =} CH 3), 1,2- di -O- phytanyl - glycero -N- ethyl - In phosphoethanolamine (general formula ^{(I) R 1 = R 2} = H, R 3 = CH ₃ C
H ₂ ), 1,2-di-O-phytanyl-glycero-phosphoethanolamine (in the general formula (I), R ¹ = R ² =
R ³ = H) and the like. In addition, diphytanylglycerophosphatidic acid, diphytanylglycerophosphatidylglycerol, diphytanylglycerophosphatidylserine, diphytanylglycerophosphatidylinositol, diphytanylglycerophosphatidic acid, which is derived from these phospholipids by a method of enzymatic reaction or chemical synthesis, is used. Tanylglycerophosphatidylsphingomyelin, lysophytanylglycerophosphocholine and the like can also be used. In the cosmetic of the present invention, these may be used alone,
You may use 2 or more types simultaneously. These phospholipids can be synthesized by the method disclosed in Japanese Patent Application No. 3-262142 or by applying it.

Liposomes containing these phospholipids as constituents are superior in heat stability and storage stability to the liposomes composed of diacyl phospholipids which are generally used in the general formula, and changes in pH and osmotic pressure. It is also very useful as a cosmetic material that is stable against physiologically active substances and the like, and is required to have stability against various coexisting compounds and long-term storage stability. In addition, this archaeal lipid is not only capable of forming stable liposomes by itself, but liposomes composed of a mixture of this dialkyl-type phospholipid and ordinary diacyl-type phospholipid also show high stability. It also has the function of strengthening the structure. Similar to conventional liposomes, these stable liposomes have an absorption effect on the skin and a long-lasting effect, and since the constituent phospholipids are derived from biological membranes, they are highly biocompatible.

Various effective substances can be added to the liposome-containing cosmetic amount of the present invention, and the effective substances can be encapsulated in liposomes. The substance that can be encapsulated in the liposome is not particularly limited, and for example,
A substance having a cosmetic effect such as a moisturizing action, a whitening action, an anti-aging action, a skin cell activating action, an ultraviolet absorption or a shielding action, or a mixture thereof can be used. Specific examples thereof include vitamin B group, vitamin C, amino acid, sugar, plant extract, urocanic acid, orotic acid, glucosamine, cyclodextrin, pyrrolidone carboxylic acid, arbutin, kojic acid, azulene, glycerin, glycyrrhetinic acid, glutathione, ε-. Water-soluble substances such as aminocaproic acid, allantoin, alginic acid, rutin, shikonin, biotin, tannic acid, urea and pantothenyl alcohol; polymeric substances such as collagen, hyaluronic acid, DNA, RNA, chondroitin sulfate, chitin and chitosan; enzymes, Peptide hormone, cell growth factor, placenta extract, ATP, cyclic nucleotide, interferon, tocopherol, carotene, ceramide, sphingolipid, royal jelly, bacterial metabolite, photosensitizer, pros Physiologically active substances such as grandin, vitamin A group, vitamin D, K; aminobenzoate derivative, salicylate derivative, benzotriazole derivative, benzophenone derivative, cinnamate derivative, imidazole derivative, indane derivative, dibenzoylmethane derivative, titanium dioxide, zinc oxide In addition to ultraviolet absorbers and shielding agents such as, glycerin and its derivatives, polyhydric alcohols, polyunsaturated fatty acids and their derivatives, mineral water and the like.

In the cosmetics of the present invention, the structural formula is used as a constituent of liposomes containing these active substances.
(I) archaeal phospholipid represented alone, or phosphatidylcholine, phosphatidylethanolamine,
It is used as a mixture with other phospholipids such as phosphatidylic acid, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, sphingomyelin and cardiolipin. When used as a mixture with other phospholipids, the use ratio of diphytanyl glycerophospholipid to other phospholipids used in the liposome is not limited, and further, in the cosmetic of the present invention, the active ingredient is liposome. If you include it in
The mixing ratio of the active ingredient and the phospholipid is not particularly limited.

The diphytanyl glycerophospholipid is
It may be in R- or S-stereoisomeric form or racemic form. In some cases, for the purpose of controlling the release / absorption of the active ingredient into the skin, it is used together with a photo-sensitive / pH-responsive phospholipid, cholesterol as a membrane stabilizing agent, and α as an antioxidant. -Tocopherol, etc., and also dicetyl phosphate as a charged substance,
Stearylamine or the like can also be added.

In the present invention, the method for preparing liposomes is not particularly limited, and depending on the purpose,
Any of the commonly used methods such as vortex method, ultrasonic method, reverse phase evaporation method, surfactant removal method, ethanol injection method, ether injection method, prevesicle method, annealing method, French press method and the like can be used. For example, when using an ultrasonic method, specifically, diphytanyl glycerophospholipid, or a mixture thereof is dissolved in chloroform and then the solvent is evaporated, and an aqueous solution containing a substance to be encapsulated in the obtained thin film or A buffer solution is added, and the mixture is vigorously stirred and then sonicated to obtain liposomes containing the active substance.

The obtained liposomes are added as they are, or after purification, washing, uniforming of particle size, etc., and then added together with a water-soluble component in a usual cosmetic production method to give the liposome-containing cosmetic of the present invention. Complete. In this case, the content of liposomes in the cosmetic is not particularly limited, but is preferably about 0.1 to 20% by weight. As the other compounding ingredients, any of those which are usually used as raw materials for cosmetics can be used.

Hereinafter, the present invention will be specifically described based on Examples, but the present invention is not limited thereto. Example 1 Preparation of Liposomes (PhyPC) First, phytol and isopropylideneglycerol are used as starting materials. And the archaeal phospholipid 1,2-di-phytanyl-glycero-3-phosphocholine (in the formula (I), R ¹
= R ² = R ³ = CH ₃ , hereinafter referred to as PhyPC) was synthesized according to the method of Japanese Patent Application No. 3-262142. That is, dihydrophytol obtained by hydrogenating phytol with Raney nickel in an ethanol solvent was treated with hydrobromic acid to obtain phytanyl bromide. This is reacted with benzylglycerol derived from isopropylideneglycerol by a conventional method in the presence of sodium hydride to give 1,2-di-O-phytanyl-3-
Obtained benzyl glycerol. Further, this 1,2-di-O-phytanyl-3-benzylglycerol was debenzylated with a palladium / carbon catalyst to give 1,2-di-O-phytanyl-glycerol, and then 2-bromoethylphosphoro-2 Treatment with chloride followed by trimethylamine gave the archaeal lipid 1,2-di-O-phytanyl-glycero-phosphocholine.

PhyPC 32.7 mg thus obtained
(40 μmol) was dissolved in 2 ml of chloroform in a 30 ml round-bottomed flask, and the solvent was distilled off using a rotary evaporator. After adding 4 ml of a buffer solution (20 mM Tris-HCl, pH 7.5) containing 10 mM vitamin C to the obtained lipid thin film and vigorously stirring with a vortex mixer, a probe-type ultrasonic oscillator (Nippon Seiki Seisakusho, US-300) was used. )Using
Sonication was performed at 10 ° C for 10 minutes to obtain a nearly transparent liposome solution. Furthermore, this liposome solution was purified by a Sephadex G-25 (trade name, manufactured by Pharmacia) column (eluted with the same buffer solution).

The particle size of the obtained PhyPC liposome is N
ICOMP MODEL 370 (trade name, manufactured by Pacific Scientific (Pacific Scientific))
The size was 23.5 nm on average, and it was confirmed by transmission electron microscopy that uniform spherical vesicles of about 25 nm were formed. The retention volume of this liposome measured by a conventional method is 0.469 ml / mmol.
Met.

Example 2 Preparation of liposome (DPPC-
PhyPC) Dipalmitoylphosphatidylcholine (Sigma)
A mixed lipid of 14.7 mg (20 μmol) manufactured by K.K., hereinafter referred to as DPPC) and 16.4 mg (20 μmol) of PhyPC was dissolved in 2 ml of chloroform to prepare a liposome with the same formulation as in Example 1. However, ultrasonic treatment was performed at 55 ° C. The average particle size of the obtained liposomes was 27.7 nm.

Comparative Example 1 Preparation of Liposomes (DPPC) Using 29.4 mg (40 μmol) of DPPC as a material, liposomes were prepared with the same formulation as in Example 1. However, ultrasonic treatment is 55 ℃
I did it in. The average particle size of the obtained liposomes is 20.5 nm.
The retention volume was 0.148 ml / mmmol, which was considerably lower than that of PhyPC.

Example 3 Evaluation of Storage Stability PhyPC liposome and DPPC liposome solution obtained in Example 1 and Comparative Example 1 (2 to 3 mol PC /
(1), pH 7.5) was allowed to stand at room temperature, and the appearance stability and the particle size change were observed to evaluate the storage stability. Table 1 shows the result.

[0025]

[Table 1]

As shown in the results below, conventionally used liposomes composed of acyl-type phospholipid DPPC are very unstable, and aggregate and fuse in less than 3 days to finally form a precipitate. It was On the other hand, the PhyPC liposomes presented by the present invention showed no significant change in particle size even when left at room temperature for 1 month, and even when left for 3 months, the appearance was almost transparent and no change was observed. Thus, it was found that the liposome composed of archaeal phospholipid is stable with time.

Example 4 Evaluation of stability against concentration gradient PhyPC liposomes obtained in Examples 1 and 2 and Comparative Example 1, DPPC-PhyPC mixed liposomes and D
The stability of the PPC liposome against the concentration gradient inside and outside the liposome was evaluated. Each liposome solution,
The mixture was diluted with various sodium chloride solutions having different concentrations, and the amount of vitamin C flowing out of the liposome was quantified by HPLC according to the concentration gradient at that time. As a standard for 100% release, 10% sodium deoxycholate was added to the same liposome diluted solution to completely destroy the liposomes, and the amount of vitamin C at that time was measured.

The relationship between the obtained salt concentration outside the liposome and the amount of vitamin C released is shown in FIG.

From this, the PhyPC liposome and D
It was found that the PPC-PhyPC mixed liposome was more stable than the conventionally used DPPC liposome against the concentration gradient inside and outside the liposome, and had a good retention ability for the internal substance.

Example 5 Evaluation of Thermal Stability The PhyPC liposomes obtained in Examples 1 and 2 and Comparative Example 1, DPPC-PhyPC mixed liposomes and D
The thermal stability of PPC liposomes was evaluated. Each purified liposome solution was diluted 10-fold with 20 mM Tris-HCl buffer (pH 7.5), and the mixture was left to stir at a predetermined temperature for 10 minutes. It was quantified by HPLC. As a standard for 100% release, 10% sodium deoxycholate was added to the same liposome diluted solution to completely destroy the liposomes, and the amount of vitamin C at that time was measured.

The relationship between the obtained temperature and the amount of vitamin C released from the liposome is shown in FIG.

From this, the PhyPC liposome and D
It can be seen that the PPC-PhyPC mixed liposome is also superior in thermal stability to the conventionally used DPPC liposome.

Example 6 Toner lotion <Components><Blended amount (wt%)> Vitamin C-containing liposome 0.5 Glycerin 6.0 Ethanol 8.0 Polyoxyethylene hydrogenated castor oil 0.8 Methyl paraoxybenzoate 0.05 Citric acid 0.05 Sodium citrate 0.07 Fragrance Suitable amount Purified water balance Of the above components, liposomes and glycerin, citric acid and sodium citrate are suspended and dissolved in purified water, and separately polyoxyethylene hydrogenated castor oil, methyl paraoxybenzoate, and flavors are dissolved in ethanol. Was solubilized in water and filtered to obtain a transparent lotion. The liposome was prepared as in Example 1.

Example 7 Cream <ingredient><blending amount (% by weight)> (Component A) Ascorbyl stearate 1.0 Acetate-α-tocopherol 0.2 Salami beeswax 4.0 Cetanol 2.0 Stearic acid 1.0 Isopropyl myristate 5.0 Lanolin 2.0 Liquid paraffin 9.0 Self-emulsifying glyceryl monostearate 3.0 Polyoxyethylene monostearate 1.5 Sorbitan propyl paraoxybenzoate 0.1 (Component B) Collagen-containing liposomes 3.0 Methyl paraoxybenzoate 0.2 Propylene glycol 5.0 Fragrance Suitable amount Purified water balance Component (A) at 80 ° C It melted by heating. Separately, the component (B) other than the fragrance was dissolved by heating, and the above component (A) was added thereto with stirring, and they were mixed sufficiently. Further, the mixture was cooled with stirring to develop a fragrance, and a milky white cream form of the present invention was obtained. The liposome was prepared in Example 1 using collagen instead of vitamin C.

[0035]

INDUSTRIAL APPLICABILITY As described above, the liposome containing the archaeal phospholipid proposed in the present invention is very useful as a cosmetic material such as long-term stability, and various effective substances are contained in the liposome. By encapsulating and incorporating it into a cosmetic, it is possible to provide a liposome-containing cosmetic having excellent absorption of the active substance and long-lasting effect.

[Brief description of drawings]

FIG. 1 is a graph showing the relationship between the salt concentration in the liposome outer solution and the amount of vitamin C released.

FIG. 2 is a graph showing the relationship between temperature and the amount of vitamin C released outside the liposome.

Claims (2)

[Claims] 1. A compound represented by the general formula (I): A cosmetic comprising a phospholipid represented by the formula (wherein R ¹ , R ² , and R ³ each represent a hydrogen atom or a lower alkyl group) and / or a liposome having a derivative thereof as a constituent. 2. The liposome internal substance is a substance or a mixture thereof having a moisturizing action, a whitening action, an antiaging action, a skin cell activating action, an ultraviolet absorbing or shielding action, or another cosmetic effect. Cosmetics.